Hyperplastic Polyps Research Articles

Combined SEPT9 and BMP3 methylation in plasma for colorectal cancer early detection and screening in a Brazilian population.

Colorectal cancer (CRC) screening can help to reduce its incidence and mortality. Noninvasive strategies, such as plasma analysis of epigenetic alterations, can constitute important biomarkers of CRC detection. This study aimed to evaluate the plasma methylation status of SEPT9 and BMP3 promoters as biomarkers for detection of CRC and its precursor lesions in a Brazilian population. Plasma samples from 262 participants of the CRC screening program of Barretos Cancer Hospital who had a positive fecal occult blood test and underwent colonoscopy and cancer patients were analyzed. Participants were grouped according to the worst lesion detected in the colonoscopy. Cell-free circulating DNA (cfDNA) was bisulfite treated followed by the analysis of SEPT9 and BMP3 methylation status using a droplet digital PCR system (ddPCR). The best methylation cutoff value for group discrimination was calculated by receiver operating characteristic (ROC) curve analysis. Among the 262 participants, 38 were diagnosed with CRC, 46 with advanced adenomas 119 with nonadvanced adenomas, three with sessile serrated lesions, and 13 with hyperplastic polyps. In 43 participants, no lesion was detected in the colonoscopy and were used as controls. The CRC group showed the highest cfDNA concentration (10.4 ng/mL). For the SEPT9 gene, a cutoff of 2.5% (AUC = 0.681) that discriminates between CRC and the control group resulted in CRC sensitivity and specificity of 50% and 90%, respectively. Concerning the BMP3 gene, a cutoff of 2.3% (AUC = 0.576) showed 40% and 90% of sensitivity and specificity for CRC detection, respectively. Combining SEPT9, BMP3 status, and age over 60 years resulted in a better performance for detecting CRC (AUC = 0.845) than the individual gene models, yielding 80% and 81% of sensitivity and specificity, respectively. The present study suggests that a combination of SEPT9 and BMP3 plasma methylation, along with age over 60 years, showed the highest performance in detecting CRC in a Brazilian population. These noninvasive biomarkers can potentially serve as useful tools for CRC screening programs.

The association between duration of and indications for proton pump inhibitor use and risk of gastric polyps.

The development of fundic gland polyps (FGPs) is the most common side effect of long-term proton pump inhibitor (PPI) use; however, the effect of drug use characteristics and their impact on the risk of other gastric polyp development remain unclear. We aimed to identify the influence of PPI administration, as well as its duration and dose, in the development of gastric polyps. A prospective cohort study was conducted on consecutive patients who underwent gastroscopy between September 2017 and August 2019. Detailed characteristics of gastric polyps, Helicobacter pylori infection, and PPI use were analyzed. Among the 2723 patients included, gastric polyps (75% FGPs, 22% hyperplastic) were detected in 16.4%, and 60% were prescribed PPI. The risk of FGPs and hyperplastic polyps according to the duration of PPI use were as follows: 2-5 years [odds ratio (95% confidence interval); 2.86 (2.00-4.11) and 2.82 (1.69-4.78)]; 6-9 years [7.42 (5.03-11.01) and 2.32 (1.05-4.78)]; ≥10 years [14.94 (10.36-21.80) and 3.52 (1.67-7.03)]. Multivariate analysis confirmed that the risk of FGPs was 17.16 (11.35-26.23) for ≥10 years of PPI use. Portal hypertension-related conditions were associated with hyperplastic polyps [4.99 (2.71-9.20)]. Duration of and indications for PPI use are the most predictive factors for the development of gastric polyps. Prolonged PPI use increases the risk of polyp development and the number of patients with polyps, which may burden endoscopic practice. Highly selected patients may require particular care despite minimal risk of dysplasia and bleeding generally.

Development and Validation of a Deep Learning-Based Histologic Diagnosis System for Diagnosing Colorectal Sessile Serrated Lesions.

The histopathologic diagnosis of colorectal sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) is of low consistency among pathologists. This study aimed to develop and validate a deep learning (DL)-based logical anthropomorphic pathology diagnostic system (LA-SSLD) for the differential diagnosis of colorectal SSL and HP. The diagnosis framework of the LA-SSLD system was constructed according to the current guidelines and consisted of 4 DL models. Deep convolutional neural network (DCNN) 1 was the mucosal layer segmentation model, DCNN 2 was the muscularis mucosa segmentation model, DCNN 3 was the glandular lumen segmentation model, and DCNN 4 was the glandular lumen classification (aberrant or regular) model. A total of 175 HP and 127 SSL sections were collected from Renmin Hospital of Wuhan University during November 2016 to November 2022. The performance of the LA-SSLD system was compared to 11 pathologists with different qualifications through the human-machine contest. The Dice scores of DCNNs 1, 2, and 3 were 93.66%, 58.38%, and 74.04%, respectively. The accuracy of DCNN 4 was 92.72%. In the human-machine contest, the accuracy, sensitivity, and specificity of the LA-SSLD system were 85.71%, 86.36%, and 85.00%, respectively. In comparison with experts (pathologist D: accuracy 83.33%, sensitivity 90.91%, specificity 75.00%; pathologist E: accuracy 85.71%, sensitivity 90.91%, specificity 80.00%), LA-SSLD achieved expert-level accuracy and outperformed all the senior and junior pathologists. This study proposed a logical anthropomorphic diagnostic system for the differential diagnosis of colorectal SSL and HP. The diagnostic performance of the system is comparable to that of experts and has the potential to become a powerful diagnostic tool for SSL in the future. It is worth mentioning that a logical anthropomorphic system can achieve expert-level accuracy with fewer samples, providing potential ideas for the development of other artificial intelligence models.

Serrated polyps

Colorectal lesions (CRLs) <10 mm found at colonoscopy tend towards "diagnose-and-leave" or "resect-and-discard" strategies based on real-time Kudo glandular pit-pattern's assessment using i-Scan. However, i-Scan has not yet been validated for Kudo's classification. We aimed to assess whether, in routine colonoscopy, i-Scan without magnification and optical enhancement (M-OE) reliably differentiates hyperplastic polyps (HPs) from other serrated lesions (SLs) and conventional adenomas (CAs), and, among SLs, HPs from sessile serrated lesions (SSLs) and traditional or unknown serrated adenomas (TSAs, USAs), in Kudo type II CRLs<10 mm, according to ASGE Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) recommended negative predictive value (NPV) threshold for adenomas. Prospectively recorded CRLs over 12 months, classified according to Kudo pit-pattern using i-Scan, were retrospectively compared with histology. Overall, 898 ≤5-mm and 704 6- to 9-mm CRLs were included. Type II pit-pattern was found in 76.6% and 38.7% of HPs and SSLs-TSAs/CAs (P<0.000001), and in 84.1% and 26.6% of SLs and CAs (P<0.000001). Among SLs, it was found in 81.9% and 86.6% of HPs and SSLs-TSAs. In CRLs≤5 mm, HPs were prevalent over other SLs (P=0.00001); in CRLs 6-9 mm, CAs were prevalent (P<0.000001). About 77% of SLs in right colon were SSLs-TSAs; 82% in left colon were HPs. PIVI ≥90% NPV threshold for adenomas was reached for CRLs 6-9mm (92.1%), nearly achieved for CRLs≤5 mm (88.2%), and not reached for SLs independently on the size. A strategy of "diagnose-and-leave" or "resect-and-discard" cannot be recommended for SLs<10 mm with Kudo type II pit-pattern using i-Scan, especially in right colon, if M-OE unavailable.

Integrated analysis of colorectal neoplasia tissue and gut microbiome associated serum metabolites for diagnosis of early-stage CRC and advanced adenoma.

e15523 Background: Detection and excision of early-stage CRC or colorectal precancerous lesions (advanced adenoma) has been recognized as an effective way to reduce CRC induced mortality. Integrating signals from both tumoral tissues and microenvironment exhibit better accuracy for tumor detection, especially for early-stage tumors. Gut microbiome carried out profound effects on initiation and progression of colorectal cancer and adenoma, and our previous findings have also revealed that gut microbiome-associated serum metabolites exhibited potential for detecting colorectal neoplasia patients. Here, we carried out an integrated analysis of both early colorectal neoplasia tissues and related gut microbiome to define their combined effect on serum metabolome and develop diagnostic test for early-stage CRC and advanced adenoma. Methods: Integrated analysis of untargeted metabolomics of serum and tissue samples and metagenome sequencing of paired fecal samples were applied to define tissue metabolome and gut microbiome variations between normal and colorectal neoplasia patients. Selected metabolic biomarkers were quantified by targeted LC-MS detection, and a diagnostic model based on the integrated serum metabolite biomarkers was established and evaluated in an independent modeling cohort. Results: Consensus participants undergoing coloscopy were enrolled. The serum-fecal matched discovery cohort includes 120 individuals, ranging from normal, non-adenoma polyp individuals to adenoma and early-stage CRC patients, and among them, resected neoplastic tissue samples were also examined. Co-relation analysis was caried out to build associations of serum metabolome with either tissue metabolome or gut microbiome enriched in early neoplasia patients. More than 100 candidate metabolic biomarkers in serum were selected and transferred to targeted metabolomics detection in an independent modeling cohort including 696 individuals (265 normal individuals, 122 with hyperplastic polyps, 155 with low-risk colorectal adenoma were assigned to the negative group; and positive group includes 136 advanced colorectal adenoma and 18 early-stage CRC patients). After feature selection, an integrated diagnostic model was established to detect early CRC and advanced adenoma, yielded an area under the curve (AUC) of 0.89 in the training set and an AUC of 0.87 (66.7% sensitivity, 90.4% specificity) in the testing set. As for advanced adenoma, the model could also achieve an AUC of 0.84 in the testing set (59.7% sensitivity, 90.4% specificity), significantly higher than previously reported fecal based FIT-DNA test and blood based Septin 9 test. Conclusions: Integrating serum metabolic biomarkers associated with both tumor tissue and colorectal neoplasia related gut microbiota could effectively detect early colorectal cancer and advanced adenoma.

Endoscopic Features According to Helicobacter pylori Infection Status

It is important to evaluate Helicobacter pylori (&lt;i&gt;H. pylori&lt;/i&gt;) infection based on endoscopic results because numerous studies have shown a link between &lt;i&gt;H. pylori&lt;/i&gt; infection and upper gastrointestinal conditions, such as gastric cancer. The association between &lt;i&gt;H. pylori&lt;/i&gt; infection and gastritis is fully described in the Kyoto classification of gastritis. Typical endoscopic findings in the absence of &lt;i&gt;H. pylori&lt;/i&gt; infection are a regular arrangement of collecting venules, fundic gland polyps, red streaks, and other similar features. By contrast, typical endoscopic findings in individuals with active &lt;i&gt;H. pylori&lt;/i&gt; infection include diffuse mucosal erythema, atrophy, intestinal metaplasia, inflated or tortuous folds, discharge of sticky mucus, mucosal nodularity, foveolar hyperplastic polyps, and/or xanthomas. Patchy mucosal redness and map-like mucosal redness are typical endoscopic findings in previously infected people. Because of its straightforward application in standard clinical practice, this categorization can reflect the risk of stomach cancer and be useful for both primary care physicians and experienced endoscopists.

Endoscopic features of lymphoid follicles in the colonic mucosa using the image enhanced endoscopy and its association with colorectal adenoma.

Lymphoid follicles hyperplasia (LH) is sometimes observed in the normal colon as small, round, yellowish-white nodules. LH is associated with food hypersensitivity and bowel symptoms and histologically characterized as intense infiltration of lymphocytes or plasmacytes. It is suggested that LH represents inflammatory immune response in the colonic mucosa. We investigated the presence of LH in the normal colonic mucosa and its association with incidence of colorectal lesions including colorectal cancer, adenoma and hyperplastic polyp. 605 participants undergoing colonoscopy for various indications were enrolled. Presence of LH in the proximal colon (appendix, cecum and the ascending colon) was observed using the blue laser imaging (BLI) endoscopy, a new generation image enhanced endoscopy (IEE) system. LH was defined as well demarcated white nodules. Elevated LH with erythema was distinguished as LH severe. Association between presence of LH and occurrence of colorectal lesions was investigated. Prevalence of all colorectal lesions and adenoma were significantly lower in LH severe group compared to the LH negative group (P = 0.0008, 0.0009, respectively). Mean number of all colorectal lesions and adenoma were also lower in LH severe group compared to the LH negative group (P = 0.005, 0.003 respectively). The logistic regression with adjustment for gender and age demonstrated that presence of LH severe held significantly lower risk of all colorectal lesions (OR = 0.48, 95%CI = 0.27-0.86) and adenoma (OR = 0.47, 95%CI = 0.26-0.86). LH in the colonic mucosa visualized by IEE is useful endoscopic finding to predict risk of colorectal adenoma.

Ileocecal valve-plasty for Crohn's disease: an endoscopic approach.

A 34-year old man had been diagnosed with Crohn’s disease over 3 years ago and had received biologic agents and enteral nutrition. Colonoscopy had shown stricture of the ileocecal orifice, and endoscopic balloon dilation had been performed on this 3 months ago. On his current presentation for reexamination, colonoscopy again showed stricture of the ileocecal orifice ([Fig. 1]) with multiple nodular hyperplastic polyps covering the area around the orifice ([Fig. 2]). Snare polypectomy was first done until the orifice appeared, then an IT2 knife was used to perform stricturotomy. The stricturotomy successfully dilated the stricture ([Fig. 3]), and as for the remaining polyps we decided to “trim” them with the electrical snare to improve the appearance of the ileocecal valve ([Fig. 4]); the procedure is called ileocecal valve-plasty ([Video 1]).

Unexpected upper gastrointestinal polyps in patients with short bowel syndrome treated with teduglutide: need for close monitoring

BackgroundTeduglutide is a GLP-2 analog indicated for the treatment of short bowel syndrome (SBS) since 2015. Its efficacy in reducing parenteral nutrition (PN) has been shown in patients with SBS. ObjectivesBecause teduglutide is a trophic factor, the aim of this study was to assess risk of developing polypoid intestinal lesions during treatment. MethodsA retrospective study was conducted in 35 patients with SBS treated with teduglutide for ≥1 y in a home PN expert center. All patients underwent ≥1 follow-up intestinal endoscopy during treatment. ResultsIn the 35 patients, the small bowel length was 74 cm (IQR: 25–100), and 23 patients (66%) had a colon in continuity. Upper and lower gastrointestinal endoscopy was performed after a mean treatment duration of 23 mo (IQR: 13–27), and polypoid lesions were found in 10 patients (6 with a colon in continuity, 4 with an end jejunostomy) and no lesion in 25 patients. In 8 out of the 10 patients, the lesion was found in the small bowel. Five of these lesions presented an aspect of hyperplastic polyp without dysplasia, and 3 of a traditional adenoma with low-grade dysplasia. ConclusionsOur study highlights the importance of performing follow-up upper and lower gastrointestinal endoscopy in SBS patients treated with teduglutide and the potential need to make changes to the recommendations with respect to treatment initiation and follow-up.

Incomplete resection rates of 4- to 20-mm non-pedunculated colorectal polyps when using wide-field cold snare resection with routine submucosal injection

Background and study aims Incomplete resection of 4- to 20-mm colorectal polyps occur frequently (> 10 %), putting patients at risk for post-colonoscopy colorectal cancer. We hypothesized that routine use of wide-field cold snare resection with submucosal injection (CSP-SI) might reduce incomplete resection rates (IRRs). Patients and methods Patients aged 45 to 80 years undergoing elective colonoscopies were enrolled in a prospective clinical study. All 4- to 20-mm non-pedunculated polyps were resected using CSP-SI. Post-polypectomy margin biopsies were obtained to determine IRRs through histopathology assessment. The primary outcome was IRR, defined as remnant polyp tissue found on margin biopsies. Secondary outcomes included technical success and complication rates. Results A total of 429 patients (median age 65 years, 47.1 % female, adenoma detection rate 40 %) with 204 non-pedunculated colorectal polyps 4 to 20 mm removed using CSP-SI were included in the final analysis. CSP-SI was technical successful in 97.5 % (199/204) of cases (5 conversion to hot snare polypectomy). IRR for CSP-SI was 3.8 % (7/183) (95 % confidence interval [CI] 2.7 %-5.5 %). IRR was 1.6 % (2/129), 16 % (4/25), and 3.4 % (1/29) for adenomas, serrated lesions, and hyperplastic polyps respectively. IRR was 2.3 % (2/87), 6.3 % (4/64), 4.0 % (6/151), and 3.1 % (1/32) for polyps 4 to 5 mm, 6 to 9 mm, < 10 mm, and 10 to 20 mm, respectively. There were no CSP-SI-related serious adverse events. Conclusions Use of CSP-SI results in lower IRRs compared to what has previously been reported in the literature for hot or cold snare polypectomy when not using wide-field cold snare resection with submucosal injection. CSP-SI showed an excellent safety and efficacy profile, however comparative studies to CSP without SI are required to confirm these results.

Transgastric laparoscopic polypectomy in giant gastric polyps not susceptible of endoscopic management: novel surgical technique and case series.

The identification of gastric polyps incidentally in endoscopies of the upper digestive tract has increased its incidence, varying between 0.5% and 23%. 10% of these polyps have symptoms, 40% are hyperplastic. We allow ourselves to propose a laparoscopic technique for the management of giant hyperplastic polyps associated with a pyloric syndrome, not susceptible to endoscopic resection. A series of patients approached by laparoscopic transgastric polypectomy due to the giant gastric polyps associated with pyloric syndrome, in Bogotá, Colombia, from January 2015 to December 2018. Seven patients, 85% female, with an average age of 51 years, who were admitted for pyloric syndrome and were taken to laparoscopic management, with an average surgical time of 42 min, intraoperative bleeding 7-8 cc, tolerance to the oral route 24 hours, no conversion, without mortality. Transgastric polypectomy for the management of benign giant gastric polyps that cannot be resected endoscopically turns out to be a feasible method, with a low rate of complications and without mortality.

Abstract LB114: Colon cancer preventive efficacy of ONC201 and naproxen alone or in combination in FAP relevant PIRC rat model

Abstract Colorectal Cancer (CRC) is the third most common cancer and leading cause of mortality in the US. While the rate of CRC incidence has steadily dropped in the last decades, recent rising trends among young adults are a major concern. Hence, preventing CRC in the general population would aid in reducing cancer mortality, especially in high-risk FAP patients for which there are no FDA approved preventive agents. Here, we evaluated TRAIL-inducing agent ONC201, alone and in combination with NSAID naproxen (NAP) for CRC prevention in PIRC rat model of FAP. PIRC rats (20 female rats/group) are bred and randomized by age into control and intervention groups. Starting at 6 weeks of age, PIRC rats were treated with ONC201 by gavage [25mg/kg; 2X/week (LD) or 50mg/kg; 1X/week (HD)]; NAP 200 ppm in AIN-76A diet [continuously or 1 week ON/OFF]; or the combination of ONC201 and NAP. Control group rats received vehicle only. Colonic polyps’ (CP) development (occurrence, number, and size) was monitored by periodic colonoscopies and upon termination at 32 weeks of age. Colonoscopy data indicated significantly fewer CPs in the HD ONC201, NAP alone dosing regimens, and combination groups. At termination, colonic tumors were harvested and subjected to histopathological evaluation. Colonic tumors were histologically classified as hyperplastic polyps, adenomas, and adenocarcinomas (ADCA). In vehicle treated rats, histological assessment showed multiplicity of 2.4±0.4 (Mean±SEM) hyperplastic polyps; 9.14±0.92 adenomas, and 2.4±0.27 ADCA. A significant decrease in the number of hyperplastic polyps (p&amp;lt;0.05) was observed in rats treated with combination of ONC201 and NAP continuous dosing regimens. LD and HD ONC201 regimens resulted in modest (11.3%, p=0.45) and significant (48.8%, p&amp;lt;0.0001) inhibition of colonic adenoma multiplicity, respectively. As anticipated, NAP dosing regimens showed 78-85% inhibition (p&amp;lt;0.0001) of adenoma multiplicity. Combination treatment showed &amp;gt;90% inhibition of adenomas. Importantly, LD ONC201 inhibited colonic ADAC multiplicity by 78.8% (p&amp;lt;0.0001) and remaining treatment groups showed no colonic ADACs. This histological data clearly showed that ONC201 (25 mg 2X/week or 50 mg 1x/week) significantly suppresses colonic tumor progression to colon adenoma and adenocarcinomas. NAP, either continuously or intermittent dosing, resulted in 85% and 78% inhibition of adenoma multiplicities, respectively, suggesting that intermittent dosing may be similarly effective for CRC prevention. Biomarker analysis suggested increased apoptosis (TRAIL, Caspase-3) and decrease in proliferation markers (PCNA, Cyclin D1). Our data warrants investigating ONC201 with NAP combination for CRC prevention in high risk FAP patients. (Supported by NCI-PREVENT 75N91019D00020-75N91020F00004) Citation Format: Venkateshwar Madka, Gopal Pathuri, Karthikkumar Venkatachalam, Srikanth Chiliveru, Yuting Zhang, Nandini Kumar, Nicole Stratton, Stanley Lightfoot, Mark S. Miller, Shizuko Sei, Chinthalapally V. Rao. Colon cancer preventive efficacy of ONC201 and naproxen alone or in combination in FAP relevant PIRC rat model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB114.

Hesperetin and Capecitabine Abate 1,2 Dimethylhydrazine-Induced Colon Carcinogenesis in Wistar Rats via Suppressing Oxidative Stress and Enhancing Antioxidant, Anti-Inflammatory and Apoptotic Actions.

Colon cancer is a major cause of cancer-related death, with significantly increasing rates of incidence worldwide. The current study was designed to evaluate the anti-carcinogenic effects of hesperetin (HES) alone and in combination with capecitabine (CAP) on 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis in Wistar rats. The rats were given DMH at 20 mg/kg body weight (b.w.)/week for 12 weeks and were orally treated with HES (25 mg/kg b.w.) and/or CAP (200 mg/kg b.w.) every other day for 8 weeks. The DMH-administered rats exhibited colon-mucosal hyperplastic polyps, the formation of new glandular units and cancerous epithelial cells. These histological changes were associated with the significant upregulation of colon Ki67 expression and the elevation of the tumor marker, carcinoembryonic antigen (CEA), in the sera. The treatment of the DMH-administered rats with HES and/or CAP prevented these histological cancerous changes concomitantly with the decrease in colon-Ki67 expression and serum-CEA levels. The results also indicated that the treatments with HES and/or CAP showed a significant reduction in the serum levels of lipid peroxides, an elevation in the serum levels of reduced glutathione, and the enhancement of the activities of colon-tissue superoxide dismutase, glutathione reductase and glutathione-S-transferase. Additionally, the results showed an increase in the mRNA expressions of the anti-inflammatory cytokine, IL-4, as well as the proapoptotic protein, p53, in the colon tissues of the DMH-administered rats treated with HES and/or CAP. The TGF-β1 decreased significantly in the DMH-administered rats and this effect was counteracted by the treatments with HES and/or CAP. Based on these findings, it can be suggested that both HES and CAP, singly or in combination, have the potential to exert chemopreventive effects against DMH-induced colon carcinogenesis via the suppression of oxidative stress, the stimulation of the antioxidant defense system, the attenuation of inflammatory effects, the reduction in cell proliferation and the enhancement of apoptosis.

Three pathologic criteria for reproducible diagnosis of colonic sessile serrated lesion versus hyperplastic polyp

Colonic SSLs are thought to predispose to ∼30% of colonic adenocarcinomas. This increased risk, compared to benign HPs, makes their distinction vitally important. However, no gold standard exists to differentiate them, and wide observer variability is reported. To better distinguish these polyps, we investigated 94 serrated polyps (53 SSLs and 41 HPs)using an easy-to-apply pathologic scoring system that combines, for the first time, three established distinguishing features: polyp morphology, location, and size. As an additional novel approach, polyp size was assessed by serrated biopsy number compared to endoscopic size. RNA expression profiling served as an additional biomarker. The considerable morphologic overlap across serrated polyps was quantitated for the first time. Interobserver variability was assessed by 8 expert gastrointestinal pathologists. By ROC analysis, polyp size by biopsy number performed best, followed by polyp location and morphology (areas under the curves [AUCs] = 85.9%, 81.2%, and 65.9%, respectively). Optimal discrimination combined all 3 features (AUC = 92.9%). For polyp size, the biopsy number proved superior to endoscopic size (AUC = 85.9% versus 55.2%, P=.001). Interobserver variability analysis yielded the highest reported Fleiss and Kappa statistics (0.879) and percent agreement (96.8%), showing great promise toward improved diagnosis. The proposed 3-criteria pathologic system, combining size by biopsy number, location, and morphology, yields an improved, easy-to-use, and highly reproducible diagnostic approach for differentiating SSLs and HPs.

A case of hyperplastic antrochoanal polyp in pediatric practice

A 14-year-old boy came to the children's ENT department with complaints of the absence of nasal breathing on the right side and sharp difficulty in nasal breathing on the opposite side. During pharyngoscopy, a neoplasm of pale pink colour was visible, elastic, without signs of bumpiness, which continued to the middle of the oropharynx. This clinical case shows that an antrochoanal polyp of this size is an exception in paediatric practice. During the surgical intervention, the part of the polyp that reached the nasopharynx and oropharynx was able to be removed with the help of Brunings forceps. Further operational tactic was standard.

Increased GS-II lectin binding and SATB2 downregulation are biological features for sessile serrated lesions and microvesicular hyperplastic polyps.

Sessile serrated lesions (SSLs) and microvesicular hyperplastic polyps (MVHPs) are colorectal lesions displaying gastric differentiation. Griffonia simplicifolia-II (GS-II) is a lectin specific to terminal α/βGlcNAc residues. Here, we assessed GS-II binding and performed immunostaining for HIK1083 (specific to terminal αGlcNAc residues), MUC5AC, MUC6, and special AT-rich sequence binding protein 2 (SATB2) in SSLs, MVHPs, and tubular adenomas (TAs). We observed MUC5AC positivity in 28 of 30 SSLs, but in only three of 23 TAs. Moreover, 24 of 30 SSLs were MUC6-positive, while none of the 23 TAs were MUC6-positive. None of the 30 SSLs or 23 TAs showed HIK1083 positivity. All 30 SSLs and 26 MVHPs were GS-II-positive, while only seven of 23 were in TAs. GS-II staining was mainly distributed in the Golgi region, but SSLs and MVHPs showed goblet cell distribution, in 20 of 30 and 19 of 26 cases, respectively. All SSLs, MVHPs, and TAs were SATB2-positive, but 21 of 30 SSLs and 12 of 26 MVHPs showed decreased staining intensity relative to adjacent mucosa, a decrease seen in only two of 23 in TAs. These results indicate overall that increased terminal βGlcNAc and decreased SATB2 expression are characteristics of SSLs and MVHPs.

Abstract 3346: Evaluation of a serum-based test integrating tumor tissue and gut microbiome derived metabolites for diagnosis of advanced colorectal adenoma

Abstract Background: Detection and endoscopic excision of colorectal precancerous lesions (advanced adenoma, AA) has been recognized as an effective way to prevent the occurrence of colorectal cancer (CRC) and reduce CRC induced mortality. Current DNA-based (mutations or methylations) tests exhibited compromised efficiency for AA diagnosis due to the late appearance of tumor-derived DNA biomarkers into stool or blood samples during tumorigenesis. Here, by integrating metabolic biomarkers associated with tumor tissue and colorectal neoplasia related gut microbiota, we established the serum metabolites-based test and examined its ability to detect advanced adenoma patients from normal, hyperplastic polyps and low-risk adenoma individuals. Methods: Consensus participants undergoing coloscopy were enrolled in this prospective study, and the result of colonoscope examination and histopathology from biopsied lesions were used as gold standard (ChiCTR2200058078). Serum metabolites were quantified by pseudo-targeted metabolomics based on LC-MS/MS method. By integrating abundances of these serum metabolites associated with tumor tissue and colorectal neoplasia related gut microbiota, a diagnostic model was established, and its performance for detecting advanced adenoma was validated using leave-one-out cross-validation. Results: In total, 803 participants, including 178 normal individuals, 167 patients with hyperplastic polyps, 203 patients with low-risk colorectal adenoma and 255 advanced colorectal adenoma patients, were enrolled in this study and subjected to the serum metabolites-based test. The diagnostic model achieved an AUC of 0.80 (95% CI: 0.77-0.83) for advanced adenoma, with a sensitivity of 44.7% at 88.9% specificity. Additionally, we also separately analyzed its performances for advanced adenoma with different histological subtypes, achieving a sensitivity of 37.0% for tubulous adenoma and a sensitivity of 53.3% for adenoma with villous structure, respectively. As for advanced adenoma with high-grade dysplasia, the model could achieve a sensitivity of 61.2%. In comparation, sensitivities of all current tests for advanced colorectal adenoma, either fecal or blood based, were less than 45% at a similar specificity. Conclusions: Based on integrating metabolic biomarkers associated with both tumor tissue and colorectal neoplasia related gut microbiota, we developed a novel blood-based test that can detect advanced colorectal adenoma with higher accuracy than all current fecal or blood-based tests. Citation Format: Jingyuan Xiang, Longsong Li, Xingting Guo, Xiaowei Li, Kai Lin, Liuyang Yang, Xudong Dai, Enqiang Linghu, Ningli Chai. Evaluation of a serum-based test integrating tumor tissue and gut microbiome derived metabolites for diagnosis of advanced colorectal adenoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3346.

Abstract 3380: Use of liquid biopsy for detection of pathogenic variants in cell-free tumor DNA from patients with precursor lesions and colorectal cancer

Abstract Background: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. The development of colorectal cancer is composed of multiple stages, starting with benign polyps in the large intestine and rectum, and gradually progress to carcinomas, providing a window of opportunity for early detection. Early diagnosis increases the survival rate of patients, thus making screening tests for precursor lesions (PL) and early-stage CRC essential for reducing the mortality rate. In this context, the early detection of tumors based on liquid biopsy could provide benefits for improving the survival rate of CRC patients and has emerged as a promising avenue for cancer screening. The aim of the study was to evaluate the presence of variants in plasma cell-free tumor DNA from patients with PL and CCR to identify diagnostic and early screening biomarkers. Material and Methods: The cell-free DNA (cfDNA) samples were obtained from plasma of patients that underwent diagnostic colonoscopy. Eight patients did not have any significant lesions (normal colonoscopy or hyperplastic polyp) and were classified as normal (N), 28 as CRC and 23 as PL - 13 as early adenomas (EA), 9 advanced adenomas (AA), and 1 sessile serrated lesion (SSL). In addition, the genomic DNA samples from 2 FFPE tumor matched pair samples were analyzed. Analysis of variants in 14 CRC associated genes was performed using Oncomine Colon cfDNA Assay and Ion Torrent PGM/S5 sequencer. Results and discussion: All variants were classified as missense or truncating and considered as pathogenic. Forty-seven variants were detected in nine genes (TP53, PIK3CA,FBXW7, APC, BRAF, GNAS, KRAS, MAP2K1, and SMAD4). TP53 gene showed the highest number of variants, comprising 53.19% of all detected variants, followed by KRAS (10.63%) and APC (8.51%). It was possible to detect the presence of at least one variant in ctDNA for 5 PL (5/23 - 21.73%) patients, including variants in 3 patients with early adenoma (3/13 - 23.07%) and 2 with advanced adenomas (2/9 - 22.22%) and fourteen CRC (14/28 - 50%). No variants were detected in patients with normal findings during colonoscopy. Concordance between detected variants in tumor tissue and plasma ctDNA (from matched samples) was observed only for two variants for CRC patients (GNAS and KRAS). Conclusion: The detection of variants in liquid biopsy demonstrates the potential for non-invasive early screening and diagnostic of CRC. Citation Format: Mariana Bisarro Dos Reis, Wellington dos Santos, Ana Carolina de Carvalho, Adhara Brandão, Adhara Brandão, Marcus Matsushita, Rui Manuel Reis, Denise Peixoto Guimarães. Use of liquid biopsy for detection of pathogenic variants in cell-free tumor DNA from patients with precursor lesions and colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3380.

Gastric inverted hyperplastic polyp with typical endoscopic feature.

A 37-year-old woman received gastroscopy for compliant of upper abdominal discomfort for six months. A polyp with size in 10 mm was found in the upper third of stomach. The polyp with a papilla-like depression in the top and smooth surface similar to surrounding non-atrophic mucosal characterized by regular arrangement of collective veins (Fig. 1A and B). Endoscopic ultrasound showed the lesion was hypo –equal echo in the mucosal layer, displayed expansive growth nature and oppressing submucosal layer (Fig. 1C). Histology of biopsy showed inflamed mucosa with submucosal atypic oxyntic gland, considering histological diagnosis of ectopic gastric glands with atypia, but adenocarcinoma of fundic gland type cannot be ruled out (Fig. 1D and E). Thus, the polyp was removed by endoscopic submucosal dissection for accurate histological diagnosis. The histology showed the benign hyperplastic glands with inverted growth manner with communication with mucosal at the top, the surround area was covered by normal oxyntic mucosa (Fig. 2), and diagnosed as gastric inverted hyperplastic polyp (GIHP). GIHPs are rare gastric polyps and typically appeared as rounded subepithelial lesions with normal overlying mucosa, more than half of cases with surface erosion, depression, or orifice exuding mucin [ [1] Kim JY Ahn S Kim KM et al. Gastric inverted polyps—distinctive subepithelial lesions of the stomach: clinicopathologic analysis of 12 cases with an emphasis on neoplastic potential. Am J Surg Pathol. 2021 May 1; 45: 680-689 Crossref PubMed Scopus (3) Google Scholar ]. GIHPs had the potential to develop adenocarcinoma, but histological diagnosis based on biopsy is challenging, endoscopic resection may be a wise choice for accurate diagnosis. Fig. 2Histology based on the resected specimen. (A) Scanning image of the lesion showed inverted growth manner; (B) Hyperplastic glands without dysplasia at high magnification. View Large Image Figure Viewer Download Hi-res image

Serrated colonic lesions. Current review

Serrated lesions, as a rule, were considered benign and were likened to hyperplastic polyps by anatomists and gastroenterologists. These views persisted until about 2010. However, recent data showed that serrated lesions can potentially transform into colorectal cancer (CRC). The World Health Organization classification identifies 4 categories of serrated lesions: hyperplastic polyps, sessile serrated lesions, traditional serrated adenoma and unclassified serrated adenomas. Sessile serrated lesions with dysplasia and traditional serrated adenomas are the most common precursors of CRC. Development of CRC from serrated lesions occurs through two different molecular pathways, namely, sporadic microsatellite instability and CpG island methylator phenotype, and the latter is considered the main mechanism inactivating serrated CRC pathway. In contrast to adenoma–carcinoma pathway, APC-inactivating mutations are rare in serrated adenomas.